Liposomes have been commonly tried for the delivery of genetic material (reviewed in Simoes, et al., Expert Opin. Drug Deliv. 2:237-254, 2005). However, they suffer from several drawbacks, including binding by serum components (Pedroso de Lima, et al., Curr. Med. Chem. 10:1221-1231, 2003), preferential absorption in endothelial cells of blood vessels (Dass and Choong, J. Control Release 113:155-163, 2006), and poor delivery systemically. Targeting moieties have allowed specific delivery to lung (Kawakami, et al., Crit. Rev. Ther. Drug Carrier Syst. 19:171-190, 2002) and liver (Kawakami, et al., Pharm. Res. 17:306-313, 2000).
The delivery of biologically active proteins using liposomes has remained more of a laboratory exercise (Sells, et al., Biotechniques 19:72-76, 78, 1995), and other methods such as virosomes have shown some superiority (Bungener, et al., Biosci. Rep. 22:323-338, 2002). Therefore, this represents an area where new methods and compositions are clearly needed.
In addition, many tissues are considered difficult to access via systemic liposomal delivery systems, including the brain, so direct injection techniques have had to be employed instead (Huynh, et al., J. Control Release 110:236-259, 2006). As local injection limits the amount of tissue that can be reached, there is a clear need for systemic delivery to the central nervous system.